Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Transplantation for Retinal Degenerations: Three-Year Outcomes Data

Abstract

Purpose : Pluripotent stem cells have the capacity for unlimited self-renewal and are a potential source of therapeutic material for regenerative medicine. We present the first long-term (exceeding 3 years) safety and tolerability data from the transplantation of human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells into patients with Stargardt macular dystrophy (SMD) and atrophic age-related macular degeneration (AMD).

Methods : Multicenter, prospective, dose-escalating studies were carried out to determine the safety and tolerability of subretinal transplantation of hESC-RPE cells (50,000–200,000) in 13 patients with SMD and 13 with atrophic AMD. Patients had advanced degeneration in study eye (best-corrected visual acuity [BCVA] ≤20/400); a cohort of three patients with better vision (≤20/100 in the study eye) was later added to both trials. Patients received systemic immunosuppression for at least 13 weeks, starting 1 week prior to surgery. Systemic and ocular outcomes were assessed by extensive examination, imaging, and laboratory studies.

Results : Of the 26 transplanted patients, 24 (n=11 AMD, median age 77 years [range: 60–89]; n=13 SMD, median age 48 years [range: 21–72]) reached a minimum follow-up of 36 months (range: 38–75); two AMD patients did not consent to participate in the long-term, follow-up study. At 3 years, no evidence of unanticipated persistent inflammation, hyperproliferation, tumor, ectopic (non-RPE) tissue, or serious stem-cell related adverse safety issues were observed. No dose-limiting toxicities were observed. Patches of increasing subretinal hyperpigmentation, many consistent with RPE (imaged by OCT and AF), were observed near the transplant site in 92% (n=24/26) of patients. BCVA, monitored as an uncontrolled safety parameter, was observed to substantially improve at years 1 and 2 in the majority of patients; however, by 3-years post-transplantation, these improvements diminished.

Conclusions : The hESC-RPE cell transplants, at all doses, seem safe and well tolerated for at least 3 years post-transplantation. Phase 2 controlled trials are planned with designs informed by these Phase 1 results.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.